Method for inhibiting the growth of pathogenic organisms with aromatic cycloaliphatic ketone-ethers



" 3,379,611 Patented Apr. 23, 1968 3,379,611 0 METHOD FOR INHIBITING THE GROWTH OF PATHOGENIC ORGANISMS WITH AROMAT- 0 Cl C H 0 C1 01 IC CYCLOALIPHATIC KETONE-ETHERS C1 C1 l l 1 Edward D. Wei], Lewiston, and Jerome Linder, Niagara 5 Falls, N.Y., assignors to Hooker Chemical Corpora- C1 0 C11 h tion, Niagara Falls, N.Y., a corporation of New York 01 C1 No Drawing. Continuation-impart of application Ser. No. 0 0

233,873, Oct. 29, 1962. This application Nov. 26, 1965, I I Ser. No. 510,061

9 Claims. (Cl. 167-32) 10 This in a continuation-in-part of our copending application Ser. No. 233,873, filed Oct. 29, 1962, now US. Patent 3,347,929.

0 o This invention relates to new and useful aromatic cyclo- I aliphatic ketone-ethers, processes for the production 01 on c on thereof, and methods for the use thereof as intermediates Cl and as pesticides. (31136-0 Ch C11 The compounds of this invention have the general formula: H

where Z is a halogen of atomic weight between 35 and O 81, and where A is selected from the group consisting II II of CZ- and -((FO)-- and where X is a substituent A C1 selected from the group consisting of halogen, nitro, alkyl, I I phenyl, alkoxy (and carboxy, and n is an integer from 0 to 5; X may in addition represent a benzo radical (CH=CHCH=CH) fused to the phenyl ring to form the naphthyl radical.

Specific examples of compounds of this invention are: 0

O O I I 0 Cl: C 7 C12 00 OH O] Ch C Cl:

Br 0 O O O 0 Cl CH 0 01 Q 1 Q a 40 0 O o 0 II I 01 c1, 0 C1: C1 C2 C1 C12 N020 o1, o1o c1,

01 on 01 on 0 01, o 01, 0100011 01 (sumo-Q0 on 010 c1,

c on

c on o 01, c1 c1 c1,

01 c1 01 0H30--o on c1-o on 70 c1-o o 0 01 c1 01 011mm),

C1 OnHu 0 0 0 1 n fo 01, Cl men fi C1: CH3

The compounds of this invention are made by contacting in the liquid phase, a ketone of the structure:

where A and Z are as previously defined, with a phenolic compound of the structure:

where X and n are as previously defined.

Preferred ketones from the standpoint of cost and availability are tetrachlorocyclopentene-3,S-dione and hexachloro-Z-cyclopentenone, though any ketone corresponding to the formula above may be used. No particular preference is had for phenols and any corresponding to the generic formula above is suitable. The preferred halogen which is substituted On the phenolic compound and on the ketone for reasons of economics and ease of synthesis of starting materials is chlorine.

There is no criticality regarding the concentration of either the ketone or phenolic compound, but the reactants are preferably used in equimolar amounts or with the ketone in excess.

The reactants will react to some degree when admixed as aforesaid, but it is preferred to conduct the reaction in the presence of about one mole of an acid acceptor (base) per mole of phenolic compound. The acid acceptor (base) is believed to form the phenolate salt of the phenolic compound, said salt being the reactive moiety. We do not wish to be held to a theory of the mechanism of the reaction; the base employed may function either as an acceptor of the liberated HX or it may serve to form the phenoxide anion or both. Suitable bases are sodium or potassium hydroxide, carbonate, phenate, sodium metal, magnesium hydroxide, calcium hydroxide, lithium hydroxide, pyridine, quinoline, triethylamine, N- methyl morpholine, N,N-dimethyl aniline, N,N-diethyl aniline, or any other basic tertiary amine. Not much more than one mole of acid acceptor (base) should be used however, because excess amounts may react with the product. Where X is carboxy, an extra mole of base is used for each X group. The reaction can be conducted from temperatures from about ambient up to about 200 degrees centigrade. At lower temperatures, the rate is too low to be practicable; and at higher temperatures, tars and byproduct materials are formed. The reaction is operable at subor superatmospheric pressures, but is preferably run at or near atmospheric pressure.

The use of a solvent is not necessary, but solvents may conveniently be employed. Excess ketone or phenolic compound may be used as a solvent. Other convenient solvents include aliphatic or aromatic hydrocarbons, chlorocarbons, ethers, alcohols, ketones, or esters.

No catalyst is necessary for the practice of this invention, although with some of the more slowly reacting phenols, such as certain nitrophenols, a catalytic amount of copper or copper salt may be found to have an accelerating effect on the rate of the reaction.

Reaction times ranging from several minutes to several hours are conveniently employed. Generally, the reaction can be terminated when titration of an aliquot shows that substantially one mole equivalent of halide has been liberated.

The compounds of this invention may be isolated by distillation or crystallization from the reaction mixture. In most cases, the salt formed by reaction of the liberated HX with the base employed may be removed by filtration or by washing the reaction mixture with Water.

The products of this invention are useful as pesticides and as chemical intermediates. As pesticides, they may be used for the control of fungi and bacteria as is hereinafter shown. As intermediates, the compounds of this invention undergo ring opening reactions with bases to form new herbicidal carboxylic acids, as follows:

Z Z: MOE

-0 z: (M=Metal cationor alkyl) COOM z X I Z Z: R R NH alkyl,aryl) Z/CONRR2 O CZ} Xn Z Z: MOH

COOM

ZC-COOM XI! 1 2 LCHZ:

and/or z C 0 NR R The preparations of the various embodiments of the invention are described hereinafter.

Example 1.-Preparation of 3-(2,4-dichlorophenoxy)- 2,4,4,5,5-pentachloro-2 cyclopentenone centrated hydrochloric acid. A solid forms, which melts at 149 to 150 degrees centigrade after crystallization from a hexane-benzene solution.

Analysis.Calcd. for Neutralization A ixture co g at of odium hydroxide 5 equivalent, 431.5. Found: Neutralization equivalent by n 1 P r S s t'trat'o w'th 0.1-N NaO t h 01 hth 1 t 1n parts of water is added to 82 parts of 2,4-d1chlorol n l H 0 p en P a em end pom phenol at C. This solution is then added to a mixture containing 82 parts of 2,4-dichlorophenol and 145 parts m 1 a of 2 441-01110 o h 0 of hexachloro-2-cyclopentene-l-one. The entire mixture P gfiz g g i en Xy) is heated on a steam bath. After 3 hours, 11.7 parts of 10 chloride were found, out of a theoretical amount of 14.6 A i t containing 117 parts of tetrachlor0-4-CyC10- The mlxtufe g g fi t Pot i ag pentene-1,3-dione and 326 parts of 2,4-dichlorophenol is $5 gz e at 3 g i added to a solution containing 51 parts of N-methylmor- 18 1 e m was W m 6 i o 15 pholine in 326 parts of 2,4-dichlorophenol. This mixture remove any salts and crystallized from hexane, giving h t d f 36 h t 100 t 110 d d parts of a. crystalline solid which melted at 70.5 to 73 1S 6.216 ours a agrees cen lgra. degrees centigrade The excess drchlorophenol 1s d1st1lled off and the resultmg Analysis calculatgd for C1 11.136702: C1, 593%. material is dissolved 1n benzene and filtered to remove Found: 59 g% any salts which formed. The benzene solution is partially In a similar manner, h followin 3- 1 .2 4 4 5 5. 20 evaporated. A crystalline solid came out which, on further pentachloro-Z-cyclopentenones were made from h crystallization from benzene, melted at 150 to 150.5 dechloro-2-cyclopentenone. grees centigrade.

Ex Aryl Group Phenol Used Base Used M.P., 0. Cl Theory Found 2 C0115 CEHEOH NaOH 66.5-67.5 51.2 51.2

s @011 EtzN on 49.3 48.9

(Et=ethyl) CH4 CH4 4 @011 EtaN- on 49.3 48.8

CH3 CH3 5 omG- CHEQOH EnN- 91-925 49.3 48.9

e o1- 010H EtgN. 91. 5-93 55.8 55.8

c1 c1 7 o1- 010H EtiN 109-10 03.1 62.6

s t-oimt-C4H40H N-methyl morpholine. 106-1005 44.0 43.5

9 Q Q .-..-do 80-82 44.7 40.0

Example 10.Reaction of 3-(2,4,5-trichlorophenoxy)-2, r Analysis.Calcd. for C H Cl O: CI, 43.6%. Found:

4,4,5,5-pentachloro-2-cyclopentenone with a base to 43.3%. prepare corresponding nng'opanmg product Example 12.Preparation of 1-phenoxy-2,4,4-trichlor0- H cyclopentene-3,5-dione Ch 01 A mixture containing 117 parts of tetrachloro-4-cyclo- G1 NaOH pentene-B-dione and 250 cc. of phenol is added to a solu- Cl Q 1101 1 tion containing 51 parts of N-methylmorpholine in 250 cc. phenol. This mixture is heated for 48 hours on a steam C1 bath. The excess phenol is distilled olr' and then the re- CC1FCC1-C=OO1GOH maining material is dissolved in 250 parts of benzene and the salts are filtered off. The benzene solution is evapo- 01 rated and the remaining contents are distilled. The boiling point of the material is 129 to 132 degrees centigrade at Cl 0.25 mm. The distilled material solidified. Melting point after crystallization from hexane, 57-9 degrees centigrade. C1 7 Analysis.Calcd. for C H Cl O C], 36.6%. Found: A mixture of 22.5 parts of compound of Example 35.9%, 7 +4000 parts of water and cubic centimeters of ten The compounds of the invention have utility as pestipercent sodium hydroxide is heated to 60 degrees centicides as well as chemical intermediates. In general, the grade. The sodium hydroxide insoluble material is filtered compounds of the invention exhibit fungicidal properties off and the resulting clear solution is acidified with con- 7 and bactericidal properties, as shown below:

7 Example 13 Example 14 Nutrient agar treated with l-phenoxy-2,4,4-trichlorocyclopentene-3,5-dione at 0.02 percent was inoculated with spores of Staphylococcus aureus and Escherichia coli bacteria. No bacterial growth occurred although the agar without the chemical supported vigorous growth of both species.

Example 15 The acid product prepared by the method outlined in Example was applied to a mixed population of seedlings of ragweed, lambsquarter, millet, and pigweed at the rate of 16 pounds per acre (dispersed in water). After three days, substantially complete kill of these weeds was observed.

What is claimed is:

1. A method for the control of pathogenic organisms selected from the group consisting of fungi and bacteria, comprising applying to the locus of said organisms a pesticidal amount of a compound of the formula 8 wherein Z is a halogen of atomic Weight between 35 and 81; A is a (CZ or a (C O) group; and X is selected from the group consisting of a radical of the formula joined to the benzene ring to form a naphthyl group therewith, halogen, nitro, alkyl of from l to 18 carbon atoms, phenyl, lower alkoxy, and carboxy; and n is from 0 to 5.

2. A method according to claim 1 wherein Z is chlorine.

3. A method according to claim 1 wherein the pathogenic organisms controlled are fungi.

4. A method according to claim 3 in which the compound applied is S-(fi-naphthoxy) -2,4,4,5,S-pentachloro-Z- cyclopentenone.

5. A method according to claim 3 in which the compound applied is 3-(p-tert-butylphenoxy)-2,4,4,5,5-penta chloro-2-cyclopentenone.

6. A method according to claim 3 in which the compound applied is 3-(pentachlorophenoxy)-2,4,4,5,5-pentachloro-2-cyclopentenone.

7. A method according to claim 3 in which the compound applied is 1-phenoxy-2,4,4-trichlorocyclopentene- 3,5-dione.

8. A method according to claim 1 wherein the pathogenic organisms are bacteria and their growth is inhibited by applying the compound to the situs thereof or to a nutrient material therefor.

9. A method according to claim 8 wherein the compound is 1 phenoxy 2,4,4 trichlorocyclopentene 3,5- dione.

References Cited Zencke et al.: Liebigs Annalen 437 86105 (1924). Roedig et al.: Liebigs Annalen 636 1-17 (1966).

ALBERT T. MEYERS, Primary Examiner.

JULIAN S. LEVITT, Examiner.

S. I. FRIEDMAN, Assistant Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent NO 3 ,379 ,611 April 23 1968 Edward D. Weil et a1 It is certified that error appears in the above identified patent and that said Letters Patent are hereby corrected as shown below:

Column 1, lines 36 to 41, the left formula should appear as same column 1, lines 42 to 46, the left formula should appear as C1 :.C1 N0 @0 C1 Column 3 lines 1 to 7 the left formula should appear as shown below: 0

Signed and sealed this 10th day of March 1970.

shown below:

shown below:

(SEAL) Attest:

EDWARD M.FLETCHER,JR. WILLIAM E. SCHUYLER, JR.

Commissioner of Patents Attesting Officer 

1. A METHOD FOR THE CONTROL OF PATHOGENIC ORGANISMS SELECTED FROM THE GROUP CONSISTING OF FUNGI AND BACTERIA, COMPRISING APPLYING TO THE LOCUS OF SAID ORGANISMS A PESTICIDAL AMOUNT OF A COMPOUND OF THE FORMULA 